Chinchilla middle-ear admittance and sound power: high-frequency estimates and effects of inner-ear modifications.
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ABSTRACT:
SUBMITTER: Ravicz ME
PROVIDER: S-EPMC3477186 | biostudies-other | 2012 Oct
REPOSITORIES: biostudies-other
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Project description:While the cochlea is considered the primary site of the auditory response to bone conduction (BC) stimulation, the paths by which vibratory energy applied to the skull (or other structures) reaches the inner ear are a matter of continued investigation. We present acoustical measurements of sound in the inner ear that separate out the components of BC stimulation that excite the inner ear via ossicular motion (compression of the walls of the ear canal or ossicular inertia) from the components that act directly on the cochlea (cochlear compression or inertia, and extra-cochlear 'third-window' pathways). The results are consistent with our earlier suggestion that the inner-ear mechanisms play a large role in bone-conduction stimulation in the chinchilla at all frequencies. However, the data also suggest the pathways that conduct vibration to the inner ear via ossicular-motion make a significant contribution to the response to BC stimulation in the 1-3 kHz range, such that interruption of these path leads to a 5 dB reduction in total stimulation in that frequency range. The mid-frequency reduction produced by ossicular manipulations is similar to the 'Carhart's notch' phenomenon observed in otology and audiology clinics in cases of human ossicular disorders. We also present data consistent with much of the ossicular-conducted sound in chinchilla depending on occlusion of the ear canal.
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Project description:The middle-ear pressure gain GMEP, the ratio of sound pressure in the cochlear vestibule PV to sound pressure at the tympanic membrane PTM, is a descriptor of middle-ear sound transfer and the cochlear input for a given stimulus in the ear canal. GMEP and the cochlear partition differential pressure near the cochlear base ΔPCP, which determines the stimulus for cochlear partition motion and has been linked to hearing ability, were computed from simultaneous measurements of PV, PTM, and the sound pressure in scala tympani near the round window PST in chinchilla. GMEP magnitude was approximately 30 dB between 0.1 and 10 kHz and decreased sharply above 20 kHz, which is not consistent with an ideal transformer or a lossless transmission line. The GMEP phase was consistent with a roughly 50-μs delay between PV and PTM. GMEP was little affected by the inner-ear modifications necessary to measure PST. GMEP is a good predictor of ΔPCP at low and moderate frequencies where PV >> PST but overestimates ΔPCP above a few kilohertz where PV ≈ PST. The ratio of PST to PV provides insight into the distribution of sound pressure within the cochlear scalae.
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Project description:The transfer function H(V) between stapes velocity V(S) and sound pressure near the tympanic membrane P(TM) is a descriptor of sound transmission through the middle ear (ME). The ME power transmission efficiency (MEE), the ratio of sound power entering the cochlea to power entering the middle ear, was computed from H(V) measured in seven chinchilla ears and previously reported measurements of ME input admittance Y(TM) and ME pressure gain G(MEP) [Ravicz and Rosowski, J. Acoust. Soc. Am. 132, 2437-2454 (2012); J. Acoust. Soc. Am. 133, 2208-2223 (2013)] in the same ears. The ME was open, and a pressure sensor was inserted into the cochlear vestibule for most measurements. The cochlear input admittance Y(C) computed from H(V) and G(MEP) is controlled by a combination of mass and resistance and is consistent with a minimum-phase system up to 27 kHz. The real part Re{Y(C)}, which relates cochlear sound power to inner-ear sound pressure, decreased gradually with frequency up to 25 kHz and more rapidly above that. MEE was about 0.5 between 0.1 and 8 kHz, higher than previous estimates in this species, and decreased sharply at higher frequencies.
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Project description:Phosphatidylinositol phosphate kinase type 1? (PIPKI?) is a key enzyme in the generation of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P(2)] and is expressed at high levels in the nervous system. Homozygous knockout mice lacking this enzyme die postnatally within 24 h, whereas PIPKI?(+/-) siblings breed normally and have no reported phenotype. Here we show that adult PIPKI?(+/-) mice have dramatically elevated hearing thresholds for high-frequency sounds. During the first postnatal week we observed a reduction of ATP-dependent Ca(2+) signaling activity in cochlear nonsensory cells. Because Ca(2+) signaling under these conditions depends on inositol-1,4,5-trisphosphate generation from phospholipase C (PLC)-dependent hydrolysis of PI(4,5)P(2), we conclude that (i) PIPKI? is primarily responsible for the synthesis of the receptor-regulated PLC-sensitive PI(4,5)P(2) pool in the cell syncytia that supports auditory hair cells; (ii) spatially graded impairment of this signaling pathway in cochlear nonsensory cells causes a selective alteration in the acquisition of hearing in PIPKI?(+/-) mice. This mouse model also suggests that PIPKI? may determine the level of gap junction contribution to cochlear development.
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Project description:ObjectivesWe sought to construct and partially characterize complementary DNA (cDNA) libraries prepared from the middle ear mucosa (MEM) of chinchillas to better understand pathogenic aspects of infection and inflammation, particularly with respect to leukotriene biogenesis and response.MethodsChinchilla MEM was harvested from controls and after middle ear inoculation with nontypeable Haemophilus influenzae. RNA was extracted to generate cDNA libraries. Randomly selected clones were subjected to sequence analysis to characterize the libraries and to provide DNA sequence for phylogenetic analyses. Reverse transcription-polymerase chain reaction of the RNA pools was used to generate cDNA sequences corresponding to genes associated with leukotriene biosynthesis and metabolism.ResultsSequence analysis of 921 randomly selected clones from the uninfected MEM cDNA library produced approximately 250,000 nucleotides of almost entirely novel sequence data. Searches of the GenBank database with the Basic Local Alignment Search Tool provided for identification of 515 unique genes expressed in the MEM and not previously described in chinchillas. In almost all cases, the chinchilla cDNA sequences displayed much greater homology to human or other primate genes than with rodent species. Genes associated with leukotriene metabolism were present in both normal and infected MEM.ConclusionsBased on both phylogenetic comparisons and gene expression similarities with humans, chinchilla MEM appears to be an excellent model for the study of middle ear inflammation and infection. The higher degree of sequence similarity between chinchillas and humans compared to chinchillas and rodents was unexpected. The cDNA libraries from normal and infected chinchilla MEM will serve as useful molecular tools in the study of otitis media and should yield important information with respect to middle ear pathogenesis.
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Project description:ObjectiveOtitis media is known to alter expression of cytokine and other genes in the mouse middle ear and inner ear. However, whole mouse genome studies of gene expression in otitis media have not previously been undertaken. Ninety-nine percent of mouse genes are shared in the human, so these studies are relevant to the human condition.MethodsTo assess inflammation-driven processes in the mouse ear, gene chip analyses were conducted on mice treated with trans-tympanic heat-killed Hemophilus influenza using untreated mice as controls. Middle and inner ear tissues were separately harvested at 6 hours, RNA extracted, and samples for each treatment processed on the Affymetrix 430 2.0 Gene Chip for expression of its 34,000 genes.ResultsStatistical analysis of gene expression compared to control mice showed significant alteration of gene expression in 2,355 genes, 11% of the genes tested and 8% of the mouse genome. Significant middle and inner ear upregulation (fold change >1.5, p<0.05) was seen in 1,081 and 599 genes respectively. Significant middle and inner ear downregulation (fold change <0.67, p<0.05) was seen in 978 and 287 genes respectively. While otitis media is widely believed to be an exclusively middle ear process with little impact on the inner ear, the inner ear changes noted in this study were numerous and discrete from the middle ear responses. This suggests that the inner ear does indeed respond to otitis media and that its response is a distinctive process. Numerous new genes, previously not studied, are found to be affected by inflammation in the ear.ConclusionWhole genome analysis via gene chip allows simultaneous examination of expression of hundreds of gene families influenced by inflammation in the middle ear. Discovery of new gene families affected by inflammation may lead to new approaches to the study and treatment of otitis media.
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Project description:Wavelength-swept optical coherence tomography (OCT) was used to scan the structure of cadaveric chinchilla ears in three dimensions with high spatial resolution and measure the sound-induced displacements of the entire OCT-visible lateral surfaces of the ossicles in the lateral-to-medial direction. The simultaneous measurement of structure and displacement allowed a precise match between the observed motion and its structural origin. The structure and measured displacements are consistent with previously published data. The coincident detailed structural and motion measurements demonstrate the presence of several frequency-dependent modes of ossicular motion, including: (i) rotation about an anteriorly-to-posteriorly directed axis positioned near the commonly defined anatomical axis of rotation that dominates at frequencies below 8 kHz, (ii) a lateral-to-medial translational component that is visible at frequencies from 2 to greater than 10 kHz, and (iii) a newly described rotational mode around an inferiorly-to-superiorly directed axis that parallels the manubrium of the malleus and dominates ossicular motion between 10 and 16 kHz. This new axis of rotation is located near the posterior edge of the manubrium. The onset of the second rotational mode leads to a boost in the magnitude of sound-induced stapes displacement near 14 kHz, and adds a half-cycle to the accumulating phase in middle-ear sound transmission. Similar measurements in one ear after interruption of the incudostapedial joint suggest the load of the cochlea and stapes annular ligament is important to the presence of the second rotational mode, and acts to limit simple ossicular translation.
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